Diagnostic value of flecainide testing in unmasking SCN5A-Related Brugada syndrome

Introduction: Provocation tests with sodium channel blockers are often required to unmask ECG abnormalities in Brugada syndrome (BrS). However, their diagnostic value is only partially established, while life-threatening ventricular arrhythmias during these tests were reported. We aimed to establish sensitivity, specificity, and safety of flecainide testing, and to predict a positive test outcome from the baseline ECG. Methods and Results: We performed 160 tests with flecainide in subjects determined to be at risk for BrS. P wave width, PQ duration, QRS width, S wave amplitude and duration in leads II-III, in addition to ST morphology and J point elevation in V1-V3 were measured before and after flecainide administration. Moreover, leads were positioned over the third intercostal space (V1(IC3)-V2(IC3)). Flecainide tests were considered positive if criteria from the First Consensus Report on BrS were fulfilled. In 64 cases, the test was positive, while 95 were negative (1 test was prematurely interrupted). The sensitivity and specificity, calculated in SCN5A-positive probands and their family members, were 77% and 80%, respectively. Baseline ECGs exhibited significant group differences in P, PQ, and QRS duration, J point elevation (leads V1-V2 and V1(IC3)-V2(IC3)), and S duration in II, but an attempt to predict the outcome of flecainide testing from these baseline ECG parameters failed. No malignant arrhythmias were observed. Conclusion: Flecainide testing is a valid and safe tool to identify SCN5A-related BrS patients. Baseline ECGs do not predict test outcomes, but point to conduction slowing as a core mechanism in BrS.